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Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism

Boag, Alisdair M.; Short, Andrea; Kennedy, Lorna J.; Syme, Hattie; Graham, Peter A.; Catchpole, Brian


Alisdair M. Boag

Andrea Short

Lorna J. Kennedy

Hattie Syme

Professor of Veterinary Clinical Pathology and Endocrinology

Brian Catchpole


Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison’s disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has implicated CTLA4 as a potential susceptibility gene. CTLA4 is an important regulator of T cell function and polymorphisms/mutations in CTLA4 have been associated with a number of autoimmune phenotypes in both humans and rodent models of autoimmunity. The aim of the current study was to undertake a case:control association study of CTLA4 promotor polymorphisms in three dog breeds, cocker spaniels, springer spaniels and West Highland white terriers (WHWT).

Polymorphisms in the CTLA4 promoter were determined by PCR and sequence-based typing. There were significant associations with three promoter haplotypes in cocker spaniels (p = 0.003). A series of SNPs were also associated with hypoadrenocorticism in cocker spaniels and springer spaniels, including polymorphisms in predicted NFAT and SP1 transcription factor binding sites.

This study provides further evidence that CTLA4 promotor polymorphisms are associated with this complex genetic disease and supports an immune mediated aetiopathogenesis of canine hypoadrenocorticism.


Boag, A. M., Short, A., Kennedy, L. J., Syme, H., Graham, P. A., & Catchpole, B. (2020). Polymorphisms in the CTLA4 promoter sequence are associated with canine hypoadrenocorticism. Canine Medicine and Genetics, 7, Article 2.

Journal Article Type Article
Acceptance Date Feb 18, 2020
Online Publication Date Mar 4, 2020
Publication Date Mar 4, 2020
Deposit Date Mar 13, 2020
Publicly Available Date Mar 13, 2020
Journal Canine Medicine and Genetics
Electronic ISSN 2662-9380
Publisher Springer Nature
Peer Reviewed Peer Reviewed
Volume 7
Article Number 2
Keywords Addison’s, Canine, CTLA-4, Hypoadrenocorticism, Promoter
Public URL
Publisher URL
Additional Information Received: 7 November 2019; Accepted: 18 February 2020; First Online: 4 March 2020; : Ethical approval was granted by The Royal Veterinary College Institutional Ethics and Welfare Committee.; : Not applicable.; : Lorna J Kennedy is Managing Editor on Canine Medicine and Genetics. However, she will not be involved in the decision-making of this paper. The other authors declare no competing interests.